Infections are caused by parasitic microorganisms such as viruses, bacteria or fungi which invade the host and rapidly reproduce. The body's natural immune system is designed to combat most infections. Some infections may become chronic, particularly if the host has a compromised immune system. Uncontrolled infections may cause serious health problems including death. Infections are frequently associated with wounds and may also occur in the locale of implanted devices such as ports, catheters, stents, artificial cartilaginous implants, orthopedic prosthetics, pacemakers, PICCs, prosthetic knee or hip implants, tooth implants, heart valves, spinal implants, and other types of plastic and/or metallic devices, to name a few. These medical devices can become infected after implanted into a patient. Long-term implants can be particularly susceptible to infection. Infection of implanted medical devices can constitute one of the most serious complications after surgery. Removing these infected medical devices can require lengthy procedures to remove and replace the old infected devices with a new device. Such procedures can involve steps such as removing the infected implant through surgical procedure, and/or administering antibiotics, waiting for any infection to heal, and then performing another surgical procedure to re-insert a new medical implant into the patient. In the case of cartilaginous implants, this may have to be repeated several times and may require administering not only a new cartilage implant but also numerous doses of antibiotics in order to enable the infection and the patient's skin to heal and then to reinsert a new artificial cartilage implant. Thus, multiple surgeries can be required. This can greatly increase procedure time and costs and can cause much discomfort to the patient. Pharmaceuticals such as antimicrobial agents and antibiotics can be used to fight infections in such cases, but there are drawbacks to the use of these agents including allergic reactions, negative interactions with other drugs, and ineffective treatment due to an increase in resistant strains of these microorganisms. Sometimes a membrane can develop over infected areas, thereby creating an impassable barrier to antibiotics.
Despite the many problems with infections of implantable medical devices, little has been done to address the cost, pain, and increased procedure time and to present effective solutions for sterilizing and/or treating infections that occur as a result of implanted medical devices. Most procedures involve removing infected devices and/or sterilizing medical devices through external application of bactericidal solutions or temperature extremes such as thermal heating or freezing, UV light, RF, microwave, or other radiation measures.
Therefore, it is desirable to provide a cost-effective, painless, efficient method for treating infections by sterilizing infected implanted medical devices which methods can overcome the problems of traditional pharmaceutical treatment, such as, for example, resistance to systemic antibiotics. The methods provided herein use irreversible electroporation to sterilize implanted medical devices, thereby treating infection in patients, providing increased treatment efficacy, and eliminating or minimizing allergic reactions, which eliminates the chance of interactions with other drugs. This could also enhance patient quality of life, which would be very beneficial for patients having extreme arthritis, for example.
What is provided herein is a method of using irreversible electroporation (IRE) to treat parts of the human body that have been subject to infection. This method avoids surgical methods that require removal surgery, a waiting period, then replacement of an infected medical device. This method can greatly improve outcomes, particularly for devices where infection may be catastrophic, i.e., a prosthetic knee or hip implant. It can also greatly improve costs and improve the longevity of implanted medical devices which are susceptible to infection, such as, for example, implantable ports. Such infection can be on or within a medical device that is implanted within a patient, as described above. Alternatively, a patient's tissue can be infected due to some other type of infection, for example, gangrene. IRE can be used to treat such infections and/or simultaneously sterilize an implanted medical device, as described herein to solve the above-mentioned problems.
Electroporation is defined as a phenomenon that makes cell membranes permeable by exposing them to certain electric pulses. As a function of the electrical parameters, electroporation pulses can have two different effects on the permeability of the cell membrane. The permeabilization of the cell membrane can be reversible or irreversible as a function of the electrical parameters used. Reversible electroporation is the process by which the cellular membranes are made temporarily permeable. The cell membrane will reseal a certain time after the pulses cease, and the cell will survive. Reversible electroporation is most commonly used for the introduction of therapeutic or genetic material into the cell. Irreversible electroporation also creates pores in the cell membrane but these pores do not reseal, resulting in cell death.
Irreversible electroporation has recently been discovered as a viable alternative for the ablation of undesired tissue. See, in particular, PCT Application No. PCT/US04/43477, filed Dec. 21, 2004. An important advantage of irreversible electroporation, as described in the above reference application, is that the undesired tissue is destroyed without creating a thermal effect. When tissue is ablated with thermal effects, not only are the cells destroyed, but the connective structure (tissue scaffold) and the structure of blood vessels are also destroyed, and the proteins are denatured. This thermal mode of damage detrimentally affects the tissue, that is, it destroys the vasculature structure and bile ducts, and produces collateral damage.
Irreversible and reversible electroporation without thermal effect to ablate tissue offers many advantages. One advantage is that it does not result in thermal damage to target tissue or other tissue surrounding the target tissue. Another advantage is that it only ablates cells and does not damage blood vessels or other non-cellular or non-living materials such as implanted medical devices.
Although the following examples discuss using the present invention and method to destroy various infectious cells, for example, such as implanted medical device-related bacteremia, that may substantially cover various implanted medical devices, persons of ordinary skill in the art will appreciate that the present devices and methods can be used to treat any undesirable cellular growth, including infectious cells, as well as to sterilize implanted medical devices.